Attenuation-based optic neuropathy detection with three-dimensional optical coherence tomography

ABSTRACT

Optical coherence tomography (OCT) scan data of a subject is acquired over a region of interest which can include an optic disc or a macula of a retina. Layer boundaries of retinal layers are identified in the OCT scan data to facilitate measurements. In one aspect, a measurement related to ratio value between a total backscattered signal intensity of one or more target layers of the retina and a total backscattered signal intensity of one or more reference layers is computed on a location-by-location basis within a region of interest of the OCT scan data. Measurements can be collected, aggregated, analyzed, and displayed in connection with other information taken or derived from the OCT scan data.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 61/759,687, filed on Feb. 1, 2013, entitled “INTEGRATEDATTENUATION-BASED OPTIC NEUROPATHY DETECTION WITH THREE-DIMENSIONALOPTICAL COHERENCE TOMOGRAPHY”, the entirety of which is incorporatedherein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This application relates generally to optical diagnostic methods andapparatus and, more specifically, to an optic neuropathy detectionmethod and apparatus utilizing optical coherence tomography.

2. Description of Related Art

Conventional diagnostics for eye disorders typically include a detailedophthalmic examination of the retina. For initial examination, an eyedoctor will view the retina through an ophthalmoscope. For a permanentrecord, the retina is typically photographed with a fundus camera. Afundus photograph directly records various anatomical features of theretina, such as the optic disc, fovea, blood vessels, and lesions. Theimaging capabilities of fundus photography may be enhanced bysupplementary techniques. A high-contrast image of retinal bloodvessels, for example, can be photographed after the injection of afluorescent dye into the bloodstream. The resulting image is referred toas a fluorescein angiogram.

More sophisticated techniques have been developed for diagnostics of theeye. One such technique is three-dimensional optical coherencetomography (3D OCT). In this technique, a light beam is directed ontothe retina. Part of the beam is back-reflected, and interferometricanalysis of the back-reflected light yields information on the structureof the retina. By varying optical parameters of the light probe,features at different depths below the surface of the retina may beanalyzed. With this process, an image of a cross-section of the retinamay be generated by scanning the optical probe along a line on theretina. By rastering the optical probe across the surface of the retina,a series of cross-sectional images may be produced. The series ofcross-sectional images may be used to characterize the 3D structure ofthe retina, and parameters, such as local retinal thickness, etc., maybe measured by 3D OCT.

Analysis of the thickness of the retina can be used to diagnose certaindiseases of the eye, such as glaucoma. One indication of the health ofthe eye can be provided by comparing the retinal thickness of thepatient's eye with reference data acquired from a population of healthyeyes. Progression of eye disease can also be monitored by measuringchanges in retinal thickness over a period of time.

For example, a conventional approach is to utilize a circumpapillaryscan to detect glaucoma and monitor a progression of glaucoma in apatient. A circle scan is performed around the optic disc at a fixeddiameter. From the scan data, a thickness of the retinal nerve fiberlayer (NFL) around the circle is measured.

Attempts have been made to derive other measurements which can beapplicable to detecting optic neuropathy, such as glaucoma.Specifically, focus has been on measurements that can indicate glaucomaprior to measurable changes in retinal layer thicknesses. In oneproposal, optical properties of the retinal NFL are calculated. Inparticular, an attenuation coefficient, which characterizes how rapidlyintensity of light is attenuated as the light propagates through amedium (e.g., a scattering or absorbing medium), is one such opticalproperty. It is suspected that changes in the attenuation coefficientsof the retinal nerve fiber layer tissue can be detected prior toobservable thinning typical with glaucoma.

However, attenuation coefficients are highly dependent on location,including in the axial direction, such that the attenuation coefficientcan vary even within a particular tissue layer. Accordingly, an averagecoefficient value, e.g. calculated over a depth or thickness of thetissue layer but corresponding to a fixed and predefined depth such asthe axial dimension length associated with a single pixel, is oftenutilized as a representative value for the tissue layer for a given X-Ylocation (A-line). Thus, this locationality of attenuation coefficientsresults in an indirect or proxy relationship to underlying physicalreality associated with optic neuropathies. For instance, theattenuation calculation described produces results which aredecorrelated from thickness. While attenuation coefficient measurementscould correlate with a diagnosis of glaucoma, a thickness-basedtechnique may be equally, and possibly more, effective.

BRIEF SUMMARY OF THE INVENTION

A simplified summary is provided herein to help enable a basic orgeneral understanding of various aspects of exemplary, non-limitingembodiments that follow in the more detailed description and theaccompanying drawings. This summary is not intended, however, as anextensive or exhaustive overview. Instead, the sole purpose of thesummary is to present some concepts related to some exemplarynon-limiting embodiments in a simplified form as a prelude to the moredetailed description of the various embodiments that follow.

In various, non-limiting embodiments, 3D OCT scan data of a subject isacquired over a region of interest which can include an optic disc or amacula of a retina. Layer boundaries of retinal layers are identified inthe 3D OCT scan data to facilitate measurements of characteristics. Inone aspect, a measurement related to ratio value between a totalbackscattered signal intensity of one or more target layers of theretina and a total backscattered signal intensity of one or morereference layers is computed on a location-by-location basis within aregion of interest of the 3D OCT scan data. Measurements can becollected, aggregated, analyzed, and displayed in connection with otherinformation taken or derived from the 3D OCT scan data.

These and other embodiments are described in more detail below.

BRIEF DESCRIPTION OF THE DRAWING

The invention may take physical form in certain parts and arrangement ofparts, embodiments of which will be described in detail in thisspecification and illustrated in the accompanying drawings which form apart hereof and wherein:

FIG. 1 illustrates an exemplary, non-limiting system for detecting andmeasuring optic neuropathies of an eye;

FIG. 2 is a flow diagram of an exemplary, non-limiting embodiment fordiagnosing and/or monitoring optic neuropathies of an eye using opticalcoherence tomography;

FIGS. 3 and 4 illustrate results of measurements on OCT scan data interms of effectiveness in diagnosing glaucoma for various stages of thedisease and locations within the retina;

FIG. 5 illustrates a schematic diagram of an exemplary, non-limitingoptical coherence tomography system in which one or more aspects ofvarious embodiments herein can be implemented; and

FIG. 6 illustrates a block diagram of an exemplary, non-limitingcomputing device or operating environment in which one or more aspectsof various embodiments described herein can be implemented.

DETAILED DESCRIPTION OF THE INVENTION

Certain terminology is used herein for convenience only and is not to betaken as a limitation on the present invention. Relative language usedherein is best understood with reference to the drawings, in which likenumerals are used to identify like or similar items. Further, in thedrawings, certain features may be shown in somewhat schematic form.

It is also to be noted that the phrase “at least one of”, if usedherein, followed by a plurality of members herein means one of themembers, or a combination of more than one of the members. For example,the phrase “at least one of a first widget and a second widget” means inthe present application: the first widget, the second widget, or thefirst widget and the second widget. Likewise, “at least one of a firstwidget, a second widget and a third widget” means in the presentapplication: the first widget, the second widget, the third widget, thefirst widget and the second widget, the first widget and the thirdwidget, the second widget and the third widget, or the first widget andthe second widget and the third widget.

Diseases such as glaucoma, multiple sclerosis (MS), etc., can present asan optic neuropathy in which nerve tissue in a retina of an eye isdestroyed. While other techniques are available to diagnose and monitoroptic neuropathies (e.g., pressure estimates within the eye, visualfield tests, optic head analyzers that measure cup-to-disc ratio, etc.),optical coherence tomography (OCT) is shown to enable earlier detectionand fine measurements of disease progression. For example, takingglaucoma as an exemplary disease that presents as an optic neuropathy,increased pressure and/or tension within the eye can cause nerve fiberaxons to kink and die and/or ganglion cells to die. Thus, over time,glaucoma causes atrophy in the nerve fiber layer (NFL), the ganglioncell layer (GCL), and the inner plexiform layer (IPL). Typically, NFLdamage assumes the form of an arcuate shape centered on an optic disc ofthe eye and extending to a more temporal location, relative to the opticdisc. GCL damage is often seen in the macula of the eye, often withinthe ring of tissue surrounding the fovea where the GCL is at or near itsthickest. The NFL and GCL damage typically presents as a thinning of thelayers in the respective areas. Conventionally, a circumpapillary scantechnique is utilized to detect glaucoma and monitor a progression ofglaucoma in a patient. In this conventional approach, a circle scan isperformed around the optic disc at a diameter of approximately 3.4 mm(specifically, in the range of 3.0 to 3.45 mm). From the scan data, athickness of the circumpapillary NFL around the circle is measured.However, an OCT scan is capable of quantifying the NFL and GCL damage,or changes in other layers, groups of layers, etc., in terms of othermeasurable parameters in addition to layer thicknesses.

According to one or more aspects described herein, a measurement derivedfrom optical properties can be utilized in connection with an OCT scan.Similar to changes in tissues thickness and/or tissue mass, opticneuropathies alter the optical properties of retinal tissues. Specificoptical properties, such as attenuation coefficients, integratedattenuation values, etc., can be measured and/or estimated for specifictissues (i.e., retinal layers) based on OCT scan data. However, theseoptical properties are related, generally monotonically, to relativebackscattering between disparate groups of tissues. Accordingly, whilethe optical properties described above have underlying physical orphysiological meanings, substantially any measured quantity whichrelates to the relative backscattering can be utilized for diagnosis ofoptic neuropathies.

In one embodiment, a method for detecting and monitoring an opticneuropathy of a retina is described herein. The method includesobtaining imaging data of a region of the retina; identifying boundariesbetween layers of the retina in the region based on the imaging data;and determining, on a location-by-location basis for at least a portionof the region of the retina, a measurement value related to a ratiovalue between a total backscattered signal intensity of one or moretarget layers of the retina and a total backscattered signal intensityof one or more reference layers to generate a set of measurement valuesfor locations in the portion of the region of the retina.

In an example, the measurement value is monotonic with respect to theratio value. For instance, the measurement value is an integratedattenuation value determined according to the following relation:

$\begin{matrix}{{{\mu_{ATT}d} = \frac{\log ( {{R/\beta} + 1} )}{2}},} & (1)\end{matrix}$

where β is modeled as a substantially constant value, R is the ratiovalue, and μ_(ATT)d is the , _s measurement value and represents a totalattenuation of light over a depth d of the retina. In some cases, d maybe effectively kept constant by, for example, integrating over a fixeddepth or taking the mean of the integration, which is mathematicallyequivalent to integrating over fixed depth except that another constant(such as β) would be made to reflect the induced scaling factor. Furtherto this example, the method can include standardizing a depth over whichthe total backscattered signal intensity of the one or more referencelayers is determined from location to location. The standardizingfacilitates maintaining as a constant value. Moreover, the ratio value Rfor a particular location, with standardization of the depth over whichthe total backscattered signal intensity of the one or more referencelayers, is given by:

$\begin{matrix}\begin{matrix}{R = \frac{T_{IRL}}{T_{ref}}} \\{{\approx \frac{\sum\limits_{z = 1}^{d_{IRL}}{T_{IRL}(z)}}{\frac{1}{d_{ref}}{\sum\limits_{z = 1}^{d_{ref}}{T_{ref}(z)}}}},}\end{matrix} & (2)\end{matrix}$

where T_(IRL)(z) is a signal intensity of a backscattered signal fromthe one or more target layers at depth z, T_(ref)(z) is a signalintensity of a backscattered signal from the one or more referencelayers at depth z, d_(IRL) is a thickness of the one or more targetlayers, and d_(ref) is a thickness of the one or more reference layers.It should be noted that in equation 2, z in the numeration refers to apixel of the inner retinal layer (IRL); whereas, z in the denominatorrefers to a pixel of the reference layer.

According to other examples, the one or more target layers include aretinal nerve fiber layer, a ganglion cell layer, an inner plexiformlayer, or combinations thereof; the one or more reference layers includea retinal pigment epithelium; and the region of the retina may includean optic disc and/or a macula of the retina. In addition, the imagingdata can comprise three-dimensional optical coherence tomography scandata. The method can additionally include displaying information derivedfrom at least one of the set of measurement values or the imaging data,wherein displaying the information comprises displaying a visualrepresentation of the set of measurement results as an overlay on imagegenerated from the imaging data. Furthermore, the method can includerespectively comparing measurement values from the set of measurementvalues to one or more thresholds; and calculating a probability of anoptic neuropathy based on comparison results. The one or more thresholdsare pre-determined from a normative database.

According to another embodiment, a method is described herein thatincludes acquiring three-dimensional optical coherence tomography (3DOCT) scan data for a region of interest of the retina; segmenting the 3DOCT scan data to identify layer boundaries between layers of the retina;calculating, based on segmented 3D OCT scan data, a set of measurementvalues over at least a portion of the region of interest on alocation-by-location basis, measurement values, of the set ofmeasurement values, being based on ratio values, for respectivelocations, between a total backscattered signal intensity of one or moretarget layers of the retina and a total backscattered signal intensityof one or more reference layers. In one example, the set of measurementvalues are a set of attenuation coefficients calculatedlocation-by-location. In another example, the set of measurement valuesare a set of integrated attenuation values calculatedlocation-by-location. The method can further include comparing the setof measurement values to normative data; and outputting a probability ofan optic neuropathy based on a result of comparing the set ofmeasurement values to normative data. Constructing the normative datacan include collecting a plurality of OCT scans on a plurality ofconfirmed normal subjects, aggregating measurements from the pluralityof OCT scans, and statistically compiling aggregated measurements. Inaddition, the method can include identifying a disease associated withthe optic neuropathy.

In yet another embodiment, an OCT imaging system is described herein.The OCT imaging system can include an imaging apparatus for capturingOCT scan data of a region of interest of a retina. In addition, the OCTimaging system can include a neuropathy analysis apparatus comprising aprocessor and a non-transitory, computer-readable medium having storedthereon on computer-executable instructions, the computer-executableinstructions causing the processor to compute, location-by-location overthe OCT scan data, a set of measurement values based on ratio values,for respective locations, between a total backscattered signal intensityof one or more target layers of the retina and a total backscatteredsignal intensity of one or more reference layers. The region of interestincludes an optic disc and a macula of the retina. The set ofmeasurement values is a set of integrated attenuation values relative tothe one or more target layers of the retina.

FIG. 1 illustrates an exemplary, non-limiting system 100 for detectingand/or measuring optic neuropathy in an eye 110. Particularly, system100 includes an imaging apparatus 120 configured to generate image data140 corresponding to a region of interest 112 of the eye 110, such asthe retina or a portion thereof for example. According to one example,the region of interest 112 can be an optic disc of the eye 110 in orderto detect optic neuropathy associated with glaucoma. In another example,imaging apparatus 120 scans a macula of the eye 110 as the region ofinterest to facilitate detection and/or monitoring of multiplesclerosis, macular degeneration, etc. A scan of the macula may also beindicative of an optic neuropathy, since the NFL fibers that connect toand from the optic disc are axons of the ganglion cells. It is also tobe appreciated that a scan of the macula can facilitate detection andmonitoring of glaucoma. In another example, imaging apparatus 120 scansboth the optic disc and macula within the same scan.

In accordance with an example, imaging apparatus 120 can be an OCTapparatus and will generally be discussed as such to facilitateexplanation of aspects provided herein. However, it is to be appreciatedthat the subject matter is not limited to application only with OCT andthat the aspects described herein can be utilized in connection withother imaging modalities such as, but not limited to, computedtomography (CT), magnetic resonance imaging (MRI), ultrasound, etc.

OCT is an imaging technique capable of acquiring sub-surface images of asubject at micrometer resolutions. For instance, in ophthalmologicalapplications, OCT is utilized to generate cross-sectional images ofportions of an eye, including the retina. In general, OCT operatesaccording to the same basic principles as ultrasound but utilizes lightas a medium whereas ultrasound utilizes sound. That is, OCT images thesubject by irradiating the subject with light and measuring a time delayand intensity of reflected light. However, light is much faster thansound. So, unlike the time delay in an ultrasound echo, the time delayof the reflected light is not directly measured. Instead, OCT utilizeslow-coherence interferometry to detect time differences corresponding todistances between structures of the subject. Particularly, alow-coherence broadband light source is split into a sample portion anda reference portion. The reference portion travels a path toward areference (i.e., a reference mirror) while the sample portion isdirected towards the subject (e.g., an eye and, specifically, theretina). When a distance traveled by the sample portion and acorresponding reflection off the subject is within a coherence length ofa distance travelled by the reference portion and its correspondingreflection, an interference pattern is generated. The interferencepattern indicates an intensity of light at a certain depth of thesubject, which in turn, facilitates generating image data pertaining tothe subject.

To derive intensity information at varying depths of the subject,several different techniques can be utilized. In one technique, referredto as time-domain OCT, the travel distance of the reference portion ismodulated to scan different depths. For example, the reference mirrorcan be oscillated to change the travel distance. Other techniques, whichcan be collectively referred to as frequency-domain OCT, do not requirealterations to the reference portion. In these techniques, variousfrequencies of light can be encoded, spatially or temporally forexample, where different detected frequencies of reflected lightcorrespond to different depths within the subject. A Fourier analysis ona received signal that represents reflected intensities at differentfrequencies generates the intensities reflected at different depths at apoint of the subject.

According to one example of a frequency-domain OCT technique (commonlyreferred to as Fourier-domain or spectral-domain OCT), a referenceinterference pattern is dispersed into individual frequency componentsby a grating or other such dispersive means. Conceptually, an array ofphotodetectors, each sensitive to a specific range of frequencies,simultaneously detects respective intensities of the frequencycomponents corresponding to different depths at a scanned point of thesubject. In conventional practice, however, typically a charge coupledevice (CCD) or complimentary metal-oxide-semiconductor (CMOS) linecamera or spectrometer is utilized and the grating physically separatesthe different wavelengths of light. In another example, referred to asswept-source OCT, a tunable light source is utilized to scan overdifferent frequencies. The intensities at each scanned frequency can becollected and transformed by a Fourier analysis to generate an intensityprofile that details intensities at various depths.

A plurality of points or locations of the region of interest 112 can bescanned by the imaging apparatus 120 to generate a plurality ofcorresponding A-scans. Each A-scan provides a respective intensityprofile within the region of interest 112 at the corresponding location.A series of A-scans can be assembled to collectively form across-sectional image of the region of interest 112, which is also knownas a B-scan. For instance, A-scans associated with points along somearbitrary path on the region of interest 112 can be aggregated togenerate a cross-sectional image, along the arbitrary path, of theregion of interest 112. According to one embodiment, the imagingapparatus 120 is directed to physically scan the region of interest 112along the arbitrary path to acquire the A-scans. In another embodiment,however, the imaging apparatus 120 acquires A-scans for an area of theregion of interest 112 (such as an entirety thereof) that contains thearbitrary path. Subsequently, a B-scan along the arbitrary path can beextracted from the A-scan information. The B-scan, generated using thistechnique, can be referred to as a virtual or simulated scan since theimaging apparatus 120 is not directly scanning the arbitrary path.

A plurality of B-scans, along parallel cross-sections for instance, canbe assembled to provide a three-dimensional (3D) scan image of thevolume of the region of interest 112. Various slices of the 3D scanimage can be computed and are typically referred to as C-scans. Forexample, C-scans corresponding to en face images of retinal layers or ofthe fundus of the eye 110 can be computed from the 3D scan image (or 3Dscan data underlying the 3D scan image).

As utilized herein, 3D scan data can refer to a set of A-scans for aregion of interest, one or more B-scans derived from A-scans of the set,one or more C-scans derived from the A-scans and B-scans, or the like.In an aspect, image data 140, provided to a neuropathy analysisapparatus 130 by the imaging apparatus 120, can be 3D scan data. It isto be appreciated that image data 140 can also include supplementaryinformation in addition to the 3D scan data. For example, the imagingapparatus 120 can be capable of acquiring a fundus image in addition toOCT image data. In such cases, the fundus image can be acquired byscanning laser ophthalmoscopy, a fundus camera, or the like. However, itis to be appreciated that the fundus image can be generated from the 3Dscan data by, for instance, summing every pixel in every A-scan.

From image data 140, and particularly the 3D scan data included therein,various measurements and quantifications can be determined. Accordingly,neuropathy analysis apparatus 130 is configured to evaluate image data140, calculate measurements, and output analysis results 150 for displayor further analysis. In one example, measurements can include layerthicknesses of individual layers (e.g., NFL, GCL, inner plexiform layer(IPL), etc.), of combinations of layers (e.g., GCL and IPL (GCL+); NFL,GCL, and IPL (GCC), etc.), or of all retinal layers. In another example,measurements can include attenuation coefficients (i.e., a measure of adegree to which light attenuates while passing through a layer) or otherimage-derived coefficient measures (e.g., polarization, possiblymeasured by polarization sensitive OCT; magnitude; phase, etc.).

However, according to an exemplary, non-limiting embodiment of theneuropathy analysis apparatus 130, the measurement derived from imagedata 140 can be an integrated attenuation measurement. The integratedattenuation measurement, according to one aspect, relates to theattenuation coefficient described above. Specifically, an estimate ofthe attenuation coefficient (μ_(ATT)) can be conventionally given by thefollowing equation:

$\begin{matrix}{{\mu_{ATT} = \frac{\log ( {{R/\beta} + 1} )}{2d}},} & (3)\end{matrix}$

where β is assumed to be a constant value, R represents a ratio valuedescribed in greater detail below, and d is a depth measure indicatingthe depth over which an average attenuation coefficient is taken toproduce the estimate. An integrated attenuation value (μ_(ATT)d) can becalculated according to the following relation:

$\begin{matrix}{{\mu_{ATT}d} = \frac{\log ( {{R/\beta} + 1} )}{2}} & (4)\end{matrix}$

Conceptually, the former relationship has units of distance⁻¹ (e.g.,mm⁻¹) and represents an average attenuation coefficient over a depth, d,such as a retinal layer. The latter relationship is unit-less andrepresents an integrated attenuation over a depth (i.e., over a layer, agroup of layers, etc.). That is, equation 3 provides a measure(attenuation coefficient) representing an average rate of attenuation(i.e., attenuation per unit distance) over some distance, d. Thedistance, over which the rate of attenuation is averaged to provide theattenuation coefficient, is typically associated with a thickness of aretinal NFL layer, for example, as glaucoma typically presents as anatrophy of this layer of the eye. In contrast, the integratedattenuation measure is not a locational property but rather an aggregateproperty or a characteristic over depth. Further, an integratedattenuation measurement can be utilized as a proportional estimate oftotal layer tissue mass due to the employment of optical properties incombination with physical properties (i.e., thickness) and, thus,potentially be more diagnostically relevant. The attenuation coefficientis a proxy of tissue density and, likely, not more effective thanconventional thickness-based analyses in detection and monitoring ofoptic neuropathies.

According to another aspect, neuropathy analysis apparatus 130 cancalculate the integrated attenuation value (μ_(ATT)d), A-line by A-line,over an entirety of image data 140. However, it is to be appreciatedthat neuropathy analysis apparatus 130 can calculate integratedattenuation values for a subset of image data 140 corresponding tospecific areas the region of interest 112 selected by a user, forexample. The specifics of the calculation are detailed below.

Neuropathy analysis apparatus 130 can utilize normative databases tofacilitate identification of optic neuropathies from the measurementstaken over image data 140. Normative databases facilitate identifyingoutlier cases while also identifying probable regions of atrophy. In oneaspect, neuropathy analysis apparatus 130 can construct normativedatabases by executing OCT scans on a large number of confirmed normalsubjects, aggregating measurements from the scans, and statisticallycompiling the results. In another aspect, normative databases alreadygenerated can be provided to neuropathy analysis apparatus 130 toutilize in connection with patient scan data and correspondingmeasurements. For example, the neuropathy analysis apparatus 130utilizes the normative databases to identify locations where thecorresponding measurement triggers thresholds (e.g., p<0.05, p<0.01,etc.). Accordingly, a display, such as an OCT-derived map, can begenerated having green areas (likely normal), yellow areas(questionable, e.g. p<0.05), and red areas (likely disease conditions,e.g. p<0.01). Here, p is a probability that a statistical nullhypothesis is not disproven and can be calculated from a comparisonagainst the normative data or via a statistical test (e.g., a binomialdistribution). Accordingly, for example, p<0.01 indicates less than aone percent chance that the samples are statistically indistinguishable.It should be appreciated that the specific values of p used in the aboveexample to determine if a pixel is green, yellow or red are merelyexamples, and other values can be used as deemed appropriate.

Thus, comparison results to the normative databases, a generated 3Dvolume corresponding to a volume of the region of interest, measurementvalues, summary statistics (e.g., mean, median, standard deviation,etc.) of measurement values, image data 140 or portion thereof, can allbe combined in total or in part to generate analysis results 150 fordisplay and/or further analysis.

For example, analysis results 150 can include display data representingvarious B-scans, C-scans, OCT-derived maps, etc. The various scans canbe accompanied by measurement results and/or typical red/yellow/greennormative analysis results. In another example, measurement results canbe represented as overlays with an OCT-derived map, such as a thicknessmap, projection image, integrated attenuation map, etc., or an imageacquired from an alternative modality (e.g., scanning laserophthalmoscopy, fundus camera, etc.).

Turning to FIG. 2, illustrated in an exemplary, non-limiting process ofutilizing 3D OCT scans to facilitate diagnosis, monitoring and/ortreatment of optic neuropathies. This process can be carried out, forexample, by system 100 described above with reference to FIG. 1. At 200,a 3D OCT scan of a region of interest of an eye of a patient isperformed. As a result of the scan, 3D OCT scan data is generated. The3D OCT scan data can include a plurality of A-scans corresponding tocoordinates (e.g., x-y coordinates) of the region of interest, B-scanscomputed from a set of A-scans, C-scans computed from A or B-scans, orcomplete 3D volume data of the region of interest. The region ofinterest can cover substantially any portion of the eye or retina of theeye including, specifically, the optic disc, the macula, or both theoptic disc and macula simultaneously. The OCT apparatus performing thescan can be any one of a time-domain OCT, spectral-domain OCT, orswept-source OCT. In addition, the 3D OCT scan data can undergopre-processing such as downsampling or a three-dimensional affinetransformation to re-orient the scan data.

At 204, layer boundaries, which are relevant for desired measurements,are detected within the 3D OCT scan data. The layer boundaries enablemeasurements, such as thickness measurements, to be calculated. Further,layer boundaries delimit regions over which attenuation calculations areintegrated. By way of example, segmentation can identify the boundariesof the retinal NFL, GCL, IPL, retinal pigment epithelium (RPE), outerplexiform layer, inner segments/outer segments (IS/OS) junction,choroid, sclera, or any other retinal layers, membranes, or boundaries.

At 206, measurements are calculated over layers of interest. Inparticular, measurements are calculated based on the 3D OCT scan data inaccordance with layer boundaries detected at 204. The measurements, asdescribed above, can include thickness measurements, attenuationcoefficient or other image-derived coefficient measures, etc. Accordingto one non-limiting, exemplary embodiment, the measurement calculatedover the layers of interest is an integrated attenuation measurementbased on equation 4 above. However, it is to be appreciated that thecalculated measurement can be a generalized or abstracted measurementderived from the integrated attenuation relationship of equation 4, asdescribed in greater detail below. In an aspect, the layers of interestcan include the NFL, GCL, GCL+, GCC, or other combinations.

At 208, measurement data is aggregated and/or integrated over anaggregation region. Aggregation, according to an aspect, can involvesummation, averaging, taking a quantile (e.g., maximum, median, minimum,etc.), or the like, of a collection of measurement values within theaggregation region. For example, the aggregation region can correspondto an entire scan area (i.e., the region of interest subject to the OCTscan); superior and/or inferior hemispheres; temporal, superior, nasal,and/or inferior quadrants; 45-degree shifted quadrants (i.e.,temporal-superior quadrant, etc.); clock hours; or any other definablesub-region of the region of interest. At 210, the measurement data canoptionally be compared to normative data as described above.

At 212, output data can be displayed. According to an aspect, thedisplay can include the measurement results and the red/yellow/green,for example, normative analysis results on an A-line by A-line basis.The display can further include representations of the aggregate results(full area and/or sub-regions), including both summary statistics (e.g.,mean and standard deviation) and normative analysis results. The outputdata can also be provided as a component within an analysis reportgeared towards glaucoma (and/or MS) detection, monitoring, or treatment.Further, the results can be displayed individually or can beco-registered and overlaid with an OCT-derived map (e.g., projectionimage, thickness map, etc.) or with another imaging modality.

Generalized Measurement for Optic Neuropathy Detection

As discussed previously, conventional approaches to diagnose glaucomainclude measuring and/or estimating a thickness of a nerve fiber layer,as a proxy for layer mass, at various retinal locations. For example,such measurements or estimations can be derived from scanning laserpolarimetry, or traditional OCT-based thickness quantification. However,as stated above, thickness is a proxy of layer mass, which can introduceinconsistency in neuropathy detection methodologies. For example, Mullerglial cells serve, in part, as retinal support structure such that evenas a mass of a retinal layer approaches zero (due to disease-relatedatrophy, for instance) in a particular location, an actual measurablethickness of a retinal layer may approach a non-zero asymptote level asopposed to going to zero. In another example, hypodense regions (i.e.,holes) within a nerve fiber layer, as imaged by OCT, have been noted tobe associated with atrophy induced by optic neuropathies. This furtherhighlights that nerve fiber layer thickness and tissue mass do not fullycorrespond. Previous work involving attenuation coefficients suggeststhat changes in tissue properties might occur before measurable changesin layer thickness. However, attenuation coefficients, as mentionedabove, suffer from a similar proxy relationship as layer thickness,albeit as a proxy to tissue density as opposed to tissue mass.Accordingly, a measurement that more closely corresponds to (i.e.,better measures or estimates) total layer mass at a given retinal x/ylocation, would be expected to perform better in terms of opticneuropathy detection.

While the measurement provided above in equation 4 is such ameasurement, the integrated attenuation measurement above can be furthergeneralized so as to be functional to a greater range of opticneuropathy detection applications. First, it is assumed that β isconstant. Accordingly, the only variable quantity in equation 4 is theratio value, R. Moreover, the logarithmic transform of equation 4 hasmonotonic properties. Therefore, from a diagnostic viewpoint, equation 4reduces to:

μ_(ATT)d≠ƒ(R)   (5),

where the function, ƒ(x), is monotonic with x. Thus, μ_(ATT)d also has amonotonic relationship to R. It is to be appreciated that many diseasedetection schemes, including receiver operating characteristic (ROC)analyses, compare values to thresholds. In such schemes, rank-order isprimarily significant. Accordingly, since a monotonic relationshipexists above, an optic neuropathy detection scheme, based on integratedattenuation, can be implemented using the ratio value, R, (or any otherfactor that is a monotonic of R) by itself That is, due to the monotonicrelationship described above, the ratio value can be used as a proxymeasurement for the integrated attenuation value, so long as β issubstantially constant. In other words, a detection scheme can beimplemented that is mathematically described according to the following:

g(μ_(ATT)d)≠R   (6)

As described above, R is a ratio value. In traditional attenuationcoefficient applications (e.g., according to equation 3), R represents aratio between a total backscattered signals from the nerve fiber layerand the retinal pigment epithelium, respectively. In other words, intraditional application, the ratio is given by the following:

$\begin{matrix}{{R = \frac{T_{NFL}}{T_{RPE}}},} & (7)\end{matrix}$

where T_(i) represents a total backscattered signal from layer i.However, as utilized herein for integrated attenuation measurements, theratio value is not so limited. For instance, the target layer is notlimited to the retinal nerve fiber layer (NFL) as with previousapplications. Other layers such as the ganglion cell layer (GCL), theinner plexiform layer (IPL), or combinations thereof, can be used inaddition to the NFL (or in combination with the NFL). Generallyspeaking, a target layer can include any retinal layer that is inner tothe reference layer (i.e., closer to a center of an eyeball relative tothe reference layer) or combinations of other retinal layers inner tothe reference layer. Further, the integrated attenuation measurementdisclosed herein is not limited to utilizing the retinal pigmentepithelium (RPE) as a reference layer. Other layers, for example, theinner plexiform layer, the outer plexiform layer, or the innersegments/outer segments (IS/OS) junction, can be utilized as thereference layer. It is also to be appreciated that combinations oflayers can be utilized as a reference. As such, for integratedattenuation measurements according to equation 4 or for glaucomadetection functions according to equation 6, the ratio value R is givenby:

$\begin{matrix}{{R = \frac{T_{IRL}}{T_{ref}}},} & (8)\end{matrix}$

where IRL refers to an inner retinal layer(s) and ref relates to thereference layer(s).

Results

FIGS. 3 and 4 illustrate various results of optic neuropathy detectionbased on the concepts described herein. These results are presented inthe form of receiver operating characteristic (ROC) maps. ROC maps, ingeneral, present data (i.e., measurements) from OCT scan data for agroup of patients in comparison to historical data of many controlsubjects in which each pixel in the resulting map represents theindividual area under the curve result from an ROC analysiscorresponding to that location. In particular, ROC maps reveal patternsin which a symptom historically manifests to indicate regions ofinterest that are reliable predictors of a condition, such as glaucoma.In the ROC maps for FIGS. 3 and 4, redder areas indicate locations forwhich the associated measurement is a good predictor of a condition,while blue regions are associated with poor predictive capabilities.

FIG. 3 depicts results for early stage glaucoma related to integratedattenuation measurements of the optic disc retinal NFL for the opticdisc. FIG. 4 depicts results for moderate stage glaucoma related tointegrated attenuation measurements of the retinal NFL for the opticdisc.

With reference to FIGS. 3 and 4, the integrated attenuation methodologygenerally yields results that offer the best aspects of the individualthickness and attenuation coefficient results on a location by locationbasis. As can be seen from the example ROC maps, in some locationsintegrated attenuation tends to share more in common withthickness-based analysis, and in other locations with attenuationcoefficient analysis. With reference to the ROC maps of the optic discshown in FIGS. 3 and 4, the integrated attenuation results show abroader region of high AROC (area under the ROC curve) levels coveringthe inferior arcuate, especially in the moderate glaucoma case (FIG. 4).It should also be noted that in early glaucoma (FIG. 3) the integratedattenuation methodology has significantly higher AROC score levels thanthe attenuation coefficient based methodology. While the ROC maps ofFIGS. 3 and 4 show the optic disc, ROC maps of other areas, such as themacula, can also be constructed.

Exemplary Optical Coherence Tomography System

Turning to FIG. 5, illustrated is an exemplary, non-limiting embodimentof an optical coherence tomography (OCT) system 500 in which one or moreaspects described above can be implemented. As shown, system 500 canperform an imaging technique used in ophthalmology to generatecross-sectional images of portions of an eye 502, such as the retina forexample.

Generally, OCT involves impinging light from a low-coherence broadbandlight source 504 onto portions of the eye 502, and observing reflectedlight to generate a cross-sectional image of those portions of the eye502. Light from the light source 504 is split by a an optical adaptor506 such as a beam splitter, fiber coupler or the like, into twoportions: a sample portion 508 that travels along a path 510 toward theeye 502, and a reference portion 512 that travels along a path 514toward a reference reflector such as a mirror 516. The sample portion508 and the reference portion 512 are at least partially reflected, andthe reflected portions combined by the optical adaptor 506 and theintensity or other quality of the combined, reflected light is sensed bya detector 520 operatively connected to transmit a signal indicative ofthe sensed quality to be received by a computer 522. When the distancetravelled by the sample portion 508 is within a coherence length of thedistance travelled by the reference portion 512, an optical interferencepattern is created, affecting the intensity of the reflected andcombined light. The intensity of the combined, reflected light variesdepending upon the properties (e.g., tissue backscattering,polarization, etc. . . . ) of the portions of the eye 502 that areilluminated by the sample portion 508. Information about such propertiesof the illuminated portion of the eye 502 can then be determined basedon the intensity of the combined, reflected light, and used to generateimage data pertaining to that illuminated portion of the eye 502.

The depth to which the sample portion 508 penetrates the eye 502 can becontrolled in the time domain by varying a distance D separating atransmitter 518 of the reference portion 512 from the mirror 516.Alternatively, the depth of penetration can be controlled in thefrequency domain by utilizing a broadband light source or alternativelysweeping the wavelength of the light source 504 over a range offrequencies. Though the distance D may be varied when depth iscontrolled in the frequency domain, such variance counterbalancessaccadic eye movements or eye shape and is not intended to controlscanning depth. Conducting a Fourier analysis on the combined, reflectedlight relates the light reflected at different frequencies to lightreflected at different depths of the eye 508. Further, the mirror 516can also be utilized to adjust penetration in a frequency-domain OCTscanner, albeit typically at a much lower rate than performed in atime-domain OCT scanner.

The sample portion 508 having a fixed penetration depth can be reflectedthrough adjustment of a mirror, lens, etc. . . . , to various differentorientations (illustrated using broken lines in FIG. 5) to illuminatedifferent spatial locations over a region of interest 524 (e.g., macula,optic disc, etc. . . . ) within the eye 502. The intensity of thecombined, reflected light (or other quality) sensed by the detector 520is transmitted to the computer 522 shown in FIG. 5 for each differentspatial location of the region of interest 524. The computer 522, whichincludes a processor for executing computer-executable instructionsstored by a non-transitory, computer-readable medium such as a harddrive, for example, stores the sensed intensities in a database alsostored on the hard drive. The database can be structured to store eachvalue of the intensity sensed by the detector 520 with a link or otherrelationship to the respective different spatial location in the regionof interest 524 from which the corresponding light was reflected.Similarly, the intensity values of light reflected from the differentspatial locations, but for a different axial penetration depth of thesample portion 508 of the light into the region of interest 524, can bestored in a separate array. The data in the plurality of arrays cancollectively be utilized by the computer 522 to generate a B-scan, forexample.

Computer 522 can include additional software and/or computer-executablecode to process intensity data and generate, for example, image data 140from FIG. 1. In addition, computer 522 can include computer-executableinstructions to carry out the functions of the neuropathy analysisapparatus 130 described above. In this regard, the neuropathy analysisapparatus 130 and the imaging apparatus 120 in FIG. 1 can be implementedby system 500 or other similarly constructed system.

Exemplary Computing Device

Referring now to FIG. 6, a high-level illustration of an exemplarycomputing device 600 that can be used in accordance with the systems andmethodologies disclosed herein is illustrated. The computing device 600includes at least one processor 602 that executes instructions that arestored in a memory 604. The instructions may be, for instance,instructions for implementing functionality described as being carriedout by one or more components discussed above or instructions forimplementing one or more of the methods described above. The processor602 may access the memory 604 by way of a system bus 606.

The computing device 600 additionally includes a data store 608 that isaccessible by the processor 602 by way of the system bus 606. Thecomputing device 600 also includes an input interface 610 that allowsexternal devices to communicate with the computing device 600. Forinstance, the input interface 6910 may be used to receive instructionsfrom an external computer device, from a user, etc. The computing device600 also includes an output interface 6712 that interfaces the computingdevice 600 with one or more external devices. For example, the computingdevice 600 may display text, images, etc. by way of the output interface612.

Additionally, while illustrated as a single system, it is to beunderstood that the computing device 600 may be a distributed system.Thus, for instance, several devices may be in communication by way of anetwork connection and may collectively perform tasks described as beingperformed by the computing device 600.

Moreover, the acts described herein may be computer-executableinstructions that can be implemented by one or more processors and/orstored on a computer-readable storage medium or media. Thecomputer-executable instructions can include a routine, a sub-routine,programs, a thread of execution, and/or the like. Still further, resultsof acts of the methodologies can be stored in a computer-readablestorage medium, displayed on a display device, and/or the like.

Moreover, the term “or” is intended to mean an inclusive “or” ratherthan an exclusive “or.” That is, unless specified otherwise, or clearfrom the context, the phrase “X employs A or B” is intended to mean anyof the natural inclusive permutations. That is, the phrase “X employs Aor B” is satisfied by any of the following instances: X employs A; Xemploys B; or X employs both A and B. In addition, the articles “a” and“an” as used in this application and the appended claims shouldgenerally be construed to mean “one or more” unless specified otherwiseor clear from the context to be directed to a singular form.

Further, as used herein, the term “exemplary” is intended to mean“serving as an illustration or example of something.”

Various functions described herein can be implemented in hardware,software, or any combination thereof. If implemented in software, thefunctions can be stored on or transmitted over as one or moreinstructions or code on a computer-readable medium. Computer-readablemedia includes both computer-readable storage media and communicationmedia including any medium that facilitates transfer of a computerprogram from one place to another. A computer-readable storage media canbe any available media that can be accessed by a computer. By way ofexample, and not limitation, such computer-readable storage media cancomprise RAM, ROM, EEPROM, CD-ROM or other optical disk storage,magnetic disk storage or other magnetic storage devices, or any othermedium that can be used to carry or store desired program code in theform of instructions or data structures and that can be accessed by acomputer. Disk and disc, as used herein, include compact disc (CD),laser disc, optical disc, digital versatile disc (DVD), floppy disk, andblu-ray disc (BD), where disks usually reproduce data magnetically anddiscs usually reproduce data optically with lasers. Further, apropagated signal is not included within the scope of computer-readablestorage media. Also, a connection can be a communication medium. Forexample, if the software is transmitted from a website, server, or otherremote source using a coaxial cable, fiber optic cable, twisted pair,digital subscriber line (DSL), or wireless technologies such asinfrared, radio, and microwave, then the coaxial cable, fiber opticcable, twisted pair, DSL, or wireless technologies such as infrared,radio and microwave are included in the definition of communicationmedium. Combinations of the above should also be included within thescope of computer-readable media.

Illustrative embodiments have been described, hereinabove. It will beapparent to those skilled in the art that the above devices and methodsmay incorporate changes and modifications without departing from thegeneral scope of the claimed subject matter. It is intended to includeall such modifications and alterations within the scope of the claimedsubject matter. Furthermore, to the extent that the term “includes” isused in either the detailed description or the claims, such term isintended to be inclusive in a manner similar to the term “comprising” as“comprising” is interpreted when employed as a transitional word in aclaim.

What is claimed is:
 1. A method for detecting and monitoring an opticneuropathy of a retina, comprising: obtaining three-dimensional imagingdata of a region of the retina; identifying boundaries between layers ofthe retina in the region based on the imaging data; and determining, ona location-by-location basis for at least a portion of the region of theretina, a measurement value related to ratio value (R) between a totalbackscattered signal intensity of one or more target layers of theretina and a total backscattered signal intensity of one or morereference layers to generate a set of measurement values for locationsin the portion of the region of the retina, wherein the measurementvalue is generally monotonic with respect to an integrated attenuationvalue (μ_(ATT)d) such that R is used as a proxy measurement forμ_(ATT)d, which is determined according to the following relation:${{\mu_{ATT}d} = \frac{\log ( {{R/\beta} + 1} )}{2}},$where β is modeled as a substantially constant value, R is the ratiovalue, and μ_(ATT)d represents a total attenuation of light over a depthd of the retina.
 2. The method of claim 1, wherein the set ofmeasurement values are a set of integrated attenuation values calculatedlocation-by-location.
 3. The method of claim 2, further comprising:standardizing a depth over which the total backscattered signalintensity of the one or more reference layers is determined fromlocation to location, wherein the standardizing facilitates maintainingβ as a substantially constant value.
 4. The method of claim 3, whereinthe ratio value R for a particular location, with standardization of thedepth over which the total backscattered signal intensity of the one ormore reference layers, is given by: $\begin{matrix}{R = \frac{T_{IRL}}{T_{ref}}} \\{{\approx \frac{\sum\limits_{z = 1}^{d_{IRL}}{T_{IRL}(z)}}{\frac{1}{d_{ref}}{\sum\limits_{z = 1}^{d_{ref}}{T_{ref}(z)}}}},}\end{matrix}$ where T_(IRL)(z) is a signal intensity of a backscatteredsignal from the one or more target layers at depth z, T_(ref)(z) is asignal intensity of a backscattered signal from the one or morereference layers at depth z, d_(IRL) is a thickness of the one or moretarget layers, and d_(ref) is a thickness of the one or more referencelayers.
 5. The method of claim 1, wherein the one or more target layersinclude a retinal nerve fiber layer, a ganglion cell layer, an innerplexiform layer, or combinations thereof.
 6. The method of claim 1,wherein the one or more reference layers include a retinal pigmentepithelium.
 7. The method of claim 1, wherein the region of the retinaincludes at least one of an optic disc or a macula of the retina.
 8. Themethod of claim 1, wherein the imaging data comprises three-dimensionaloptical coherence tomography scan data.
 9. The method of claim 1,further comprising displaying information derived from at least one ofthe set of measurement values or the imaging data.
 10. The method ofclaim 9, wherein displaying the information comprises displaying avisual representation of the set of measurement values as an overlay onimage generated from the imaging data.
 11. The method of claim 1,further comprising: respectively comparing measurement values from theset of measurement values to one or more thresholds; and calculating aprobability of an optic neuropathy based on comparison results.
 12. Themethod of claim 11, wherein the one or more thresholds arepre-determined from a normative database.
 13. A method for detecting andmonitoring an optic neuropathy of a retina, comprising: acquiringimaging data for a region of interest of the retina; segmenting theimaging data to identify layer boundaries between layers of the retina;and calculating, based on segmented imaging data, a set of integratedattenuation values over at least a portion of the region of interest ona location-by-location basis, integrated attenuation values (μ_(ATT)d),of the set of integrated attenuation values, being based on ratiovalues, for respective locations, between a total backscattered signalintensity of one or more target layers of the retina and a totalbackscattered signal intensity of one or more reference layers, whereineach of the integrated attenuation values is determined according to thefollowing relation:${{\mu_{ATT}d} = \frac{\log ( {{R/\beta} + 1} )}{2}},$where β is modeled as a substantially constant value, R is the ratiovalue, and μ_(ATT)d represents a total attenuation of light over a depthd of the retina.
 14. The method of claim 13, wherein the imaging data isthree-dimensional optical coherence tomography (3D OCT) scan data. 15.The method of claim 13, further comprising: comparing the set ofintegrated attenuation values to normative data; and outputting aprobability of an optic neuropathy based on a result of comparing theset of integrated attenuation values to normative data.
 16. The methodof claim 15, further comprising constructing the normative data by:collecting a plurality of OCT scans on a plurality of confirmed normalsubjects, aggregating measurements from the plurality of OCT scans, andstatistically compiling aggregated measurements.
 17. A method fordetecting and monitoring an optic neuropathy of a retina, comprising:obtaining imaging data of a region of the retina; identifying boundariesbetween layers of the retina in the region based on the imaging data;determining, on a location-by-location basis for at least a portion ofthe region of the retina, a measurement value related to ratio value (R)between a total backscattered signal intensity of one or more targetlayers of the retina and a total backscattered signal intensity of oneor more reference layers to generate a set of measurement values forlocations in the portion of the region of the retina; respectivelycomparing integrated attenuation values from the set of integratedattenuation values to one or more thresholds; and calculating aprobability of an optic neuropathy based on comparison results.
 18. Themethod of claim 17, wherein the one or more thresholds arepre-determined from a normative database.
 19. The method of claim 17,further comprising: standardizing a depth over which the totalbackscattered signal intensity of the one or more reference layers isdetermined from location to location, wherein the standardizingfacilitates maintaining β as a substantially constant value.
 20. Themethod of claim 19, wherein the ratio value R for a particular location,with standardization of the depth over which the total backscatteredsignal intensity of the one or more reference layers, is given by:$\begin{matrix}{R = \frac{T_{IRL}}{T_{ref}}} \\{{\approx \frac{\sum\limits_{z = 1}^{d_{IRL}}{T_{IRL}(z)}}{\frac{1}{d_{ref}}{\sum\limits_{z = 1}^{d_{ref}}{T_{ref}(z)}}}},}\end{matrix}$ where T_(IRL)(z) is a signal intensity of a backscatteredsignal from the one or more target layers at depth z, T_(ref)(z) is asignal intensity of a backscattered signal from the one or morereference layers at depth z, d_(IRL) is a thickness of the one or moretarget layers, and d_(ref) is a thickness of the one or more referencelayers.
 21. The method of claim 17, wherein the one or more targetlayers include a retinal nerve fiber layer, a ganglion cell layer, aninner plexiform layer, or combinations thereof.
 22. The method of claim17, wherein the one or more reference layers include a retinal pigmentepithelium.
 23. The method of claim 17, wherein the region of the retinaincludes at least one of an optic disc or a macula of the retina. 24.The method of claim 17, wherein the imaging data comprisesthree-dimensional optical coherence tomography scan data.
 25. The methodof claim 17, further comprising displaying information derived from atleast one of the set of measurement values or the imaging data.
 26. Themethod of claim 17, wherein the integrated attenuation value isgenerally monotonic with respect to the ratio value.